7B5O

Cryo-EM structure of the human CAK bound to ICEC0942 at 2.5 Angstroms resolution

Summary for 7B5O

• Entry DOI: 10.2210/pdb7b5o/pdb
• EMDB information: 11823 11828 12042
• Descriptor: CDK-activating kinase assembly factor MAT1, Cyclin-H, Cyclin-dependent kinase 7, ... (5 entities in total)
• Functional Keywords: kinase, protein complex, small molecules inhibitor, cdk-activating kinase, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 119873.40

Authors

Greber, B.J.,Remis, J.,Ali, S.,Nogales, E. (deposition date: 2020-12-05, release date: 2021-02-10, Last modification date: 2024-05-01)

Primary citation

Greber, B.J.,Remis, J.,Ali, S.,Nogales, E.
2.5 angstrom -resolution structure of human CDK-activating kinase bound to the clinical inhibitor ICEC0942.
Biophys.J., 120:677-686, 2021

PubMed Abstract: The human CDK-activating kinase (CAK), composed of CDK7, cyclin H, and MAT1, is involved in the control of transcription initiation and the cell cycle. Because of these activities, it has been identified as a promising target for cancer chemotherapy. A number of CDK7 inhibitors have entered clinical trials, among them ICEC0942 (also known as CT7001). Structural information can aid in improving the affinity and specificity of such drugs or drug candidates, reducing side effects in patients. Here, we have determined the structure of the human CAK in complex with ICEC0942 at 2.5 Å-resolution using cryogenic electron microscopy. Our structure reveals conformational differences of ICEC0942 compared with previous X-ray crystal structures of the CDK2-bound complex, and highlights the critical ability of cryogenic electron microscopy to resolve structures of drug-bound protein complexes without the need to crystalize the protein target.

PubMed: 33476598
DOI: 10.1016/j.bpj.2020.12.030

Experimental method

ELECTRON MICROSCOPY (2.5 Å)